Rhabdomyosarcoma in low- and middle-income countries: A report from the Asociacion de Hemato-oncología Pediatrica de Centro América (AHOPCA).

This report describes the results of an observational study dedicated to rhabdomyosarcoma developed by the Asociación de Hemato-oncología Pediatrica de Centro América (AHOPCA) between 2001 and 2018. Overall, 337 previously untreated patients < 18 years old were included in the analysis; 58% had unresected disease, and 19% were metastatic at diagnosis. With a median follow-up of 6.6 years, five-year event-free and overall survival rates were 30% and 33%, respectively. Local progression/relapse was the main cause of treatment failure.

Barriers to effective treatment of pediatric solid tumors in middle-income countries: can we make sense of the spectrum of nonbiologic factors that influence outcomes?

BACKGROUND: The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs. METHODS: An ecologic model centered on pediatric sarcoma and expanded to country as the environment was used as a benchmark for studying the delivery of solid tumor care in MICs. Data on resources were gathered from 7 centers that were members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data were available, were retrieved from hospital-based cancer registries for 6 of the 7 centers, and were analyzed by country. Patients who were diagnosed from January 1, 2000 to December 31, 2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. To explore correlations between resources and outcomes, a pilot performance index was created. RESULTS: The analyses identified specific deficits in human resources, communication, quality, and infrastructure. The treatment abandonment rate, the proportion of metastatic disease at diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from 15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment abandonment rate correlated inversely with health economic expenditure per capita (r = -0.86; P = .03) and life expectancy at birth (r = -0.93; P = .007). The 4-year AOS rate correlated inversely with the mortality rate among children aged <5 years (r = -0.80; P = 0.05) and correlated directly with the pilot performance index (r = 0.98; P = 0.005). CONCLUSIONS: Initiatives to improve the effectiveness of treatment for pediatric solid tumors in MICs are warranted, particularly for pediatric sarcomas. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive, multidisciplinary teams are identified as keystones in Central America. A measure that meaningfully describes performance in delivering pediatric cancer care is feasible and needed to advance comparative, prospective analysis of pediatric cancer care and to define resource clusters internationally.

Pediatric sarcoma in Central America: outcomes, challenges, and plans for improvement.

BACKGROUND: Children with cancer in middle-income countries have inferior outcomes compared with similar children in high-income countries. The magnitude and drivers of this survival gap are not well understood. In the current report, the authors sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. METHODS: A retrospective review was conducted of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma (STS) between January 1, 2000 and December 31, 2009 were included. Survival analyses were performed first using standard definitions of overall survival (OS) and event-free survival (EFS) and then with abandonment included as an event (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785 new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175 diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was high, particularly among patients with extremity bone sarcomas (osteosarcoma, 30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced a first event, 59% had either recurrent or progressive disease. The 4-year OS rate (±standard error) was 40% ± 3%, and the EFS rate was 30% ± 2%; however, these rates decreased further to 31% ± 2% and 24% ± 2%, respectively, when abandonment was taken into account. CONCLUSIONS: The current results indicated that high rates of metastases and treatment abandonment and difficulty with upfront treatment effectiveness are important contributors to the poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes.

Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric fever in El Salvador.

BACKGROUND: Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. METHOD: This prospective cohort study included children aged 0-16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. FINDINGS: Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0-20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0-3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09-8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03-1.81; P = 0.031) and in families with an annual household income

Microbiology and mortality of pediatric febrile neutropenia in El Salvador.

BACKGROUND: Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. METHODS: We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. RESULTS: Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. CONCLUSIONS: In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions.

Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador.

BACKGROUND: Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. METHODS: We describe predictors of survival for children in El Salvador with ALL. We included patients <16 years diagnosed with ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). RESULTS: 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10×10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. CONCLUSION: Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies.